1. Field of the Invention
The present invention relates to a transdermal therapeutic system (TTS) that is essentially composed of two compartments and that is provided with activatable oversaturation and controlled permeation promotion. The invention more particularly relates to a TTS wherein an oversaturated active substance solution is produced in an active-substance-containing polymer matrix when the system is applied to the skin, caused by the controlled supply of one or more substances promoting the permeation of the pharmaceutical active substance (permeation enhancers). The present invention further relates to the two compartments that are assembled to form the transdermal therapeutic system according to the invention and to the production of said transdermal therapeutic system from said two compartments.
2. Description of the Prior Art
In practice, it is often difficult to realise the permeation of medicinal active substances through the skin into the blood circulation with the aim of attaining physiologically or therapeutically effective plasma levels or systemic pharmacodynamic effects. The reason for this lies in the skin as such, which, due to its structure and function, constitutes an effective permeation barrier for transdermally applied substances. In order to nevertheless achieve permeation rates with which physiologically or therapeutically active plasma levels can be achieved, the following three methods are predominantly used in practice:                1. addition of substances promoting the permeation of the active substance, so-called permeation enhancers;        2. application of electric current (iontophoresis) and/or ultrasound (phonophoresis); and        3. the use of release systems wherein the active substance is present at a concentration that exceeds its solubility limit in the corresponding vehicles (oversaturated systems).        
Other possibilities of improving the transdermal administration of an active substance, such as the use of so-called prodrugs, whose physicochemical properties are more favourable for skin permeation (inter alia, higher lipophilicity), play only a minor part in the development of transdermal administration systems.
However, the methods most frequently used in practice in order to improve the transdermal permeation of active substances involve considerable drawbacks too.
The essential disadvantage in adding permeation enhancers is that the latter, upon application of the release system, leave the system in an uncontrolled manner and, especially in the initial phase of application, very rapidly since said enhancers are, as a rule, readily volatile organic compounds. This uncontrolled overdosage of permeation enhancers (enhancer dose dumping) frequently causes skin irritation. In addition, incorporation of permeation enhancers in the matrix of transdermal therapeutic systems often leads to stability problems since the active substance may interact with the permeation enhancer.
The particular disadvantage of iontophoresis and phonophoresis lies, above all, in their skin irritation potential since both electric current and ultrasound interfere with the skin's barrier function more strongly than chemical permeation enhancers.
Systems oversaturated with active substance have a disadvantage in that they are only metastable and in that the recrystallization processes taking place in the active-substance-containing matrix may lead to a reduction of the bioavailability of the active substance, as well as to an adverse effect on the adhesive power of the transdermal therapeutic systems.
Satisfactory compromise solutions are known whereby oversaturation of the active substance present in the polymer matrix of a transdermal therapeutic system can be maintained as high as possible, while at the same time maintaining it as stable as required.